Optimal management of EGFR-mutant non-small cell lung cancer with disease progression on ﬁ rst-line tyrosine kinase inhibitor therapy

Bin-Chi Liao (1, 2, 3), Chia-Chi Lin (1, 4), Jih-Hsiang Lee (1, 5), James Chih-Hsin Yang (1, 2, 3, 6)
(1) Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
(2) National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan
(3) Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
(4) Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan
(5) Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
(6) Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan

The first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, and the second-generation EGFR-TKI, afatinib, have all been approved as standard first-line treatments for advanced EGFR-mutant non-small cell lung cancer (NSCLC) based on superior progression-free survival results compared to platinum doublet chemotherapy regimens. Acquired resistance to an EGFR-TKI inevitably develops after a period of effective drug treatment. After tumor progression, many combination therapy regimens that include an EGFR-TKI, or EGFR-TKI monotherapy, have been tested in prospective trials with the aim of extending survival. Third-generation EGFR-TKIs such as osimertinib have been developed with the aim of overcoming the effects of EGFR T790M resistance mutation, which occurs in half of the patients with disease progression on EGFR-TKI therapy. Osimertinib has become the standard treatment in patients for whom tumor re-biopsy reveals an acquired EGFR T790M mutation following EGFR-TKI therapy. Other third-generation EGFRTKIs, such as olmutinib, EGF816, and ASP8273, are still in the trial phase.